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Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/jspui/handle/10054/3994

Title: Perturbation of microtubule polymerization by quercetin through tubulin binding: A novel mechanism of its antiproliferative activity
Authors: GUPTA, K
PANDA, D
Keywords: cancer-cells
conformational states
kinetic stabilization
colchicine complex
natural-products
antitumor action
dynamics
flavonoids
suppression
protein
Issue Date: 2002
Publisher: AMER CHEMICAL SOC
Citation: BIOCHEMISTRY, 41(43), 13029-13038
Abstract: The dietary flavonoid quercetin has a broad range of biological activities, including potent antitumor activity against several types of tumors. Recently, it has been shown that quercetin inhibits cancer cells proliferation by depleting cellular microtubules and perturbing cellular microtubule functions. However, the direct interactions of quercetin with tubulin and microtubules have not been examined so far. Here, we found that quercetin inhibited polymerization of microtubules and depolymerized microtubules made from purified tubulin in vitro. The binding of quercetin with tubulin was studied using quercetin fluorescence and intrinsic tryptophan fluorescence of tubulin. Quercetin bound to tubulin at a single site with a dissociation constant of 5-7 muM, and it specifically inhibited colchicine binding to tubulin but did not bind at the vinblastine site. In addition, quercetin perturbed the secondary structure of tubulin, and the binding of quercetin stimulated the intrinsic GTPase activity of soluble tubulin. Further, quercetin stabilized tubulin against decay and protected two cysteine residues of tubulin toward chemical modification by 5,5'-dithiobis-2-nitrobenzoic acid. Our data demonstrated that the binding of quercetin to tubulin induces conformational changes in tubulin and a mechanism through which quercetin could perturb microtubule polymerization dynamics has been proposed. The data suggest that quercetin inhibits cancer cells proliferation at least in part by perturbing microtubule functions through tubulin binding.
URI: http://dx.doi.org/10.1021/bi025952r
http://dspace.library.iitb.ac.in/xmlui/handle/10054/3994
http://hdl.handle.net/10054/3994
ISSN: 0006-2960
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